Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents (Articolo in rivista)

Type
Label
  • Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1021/jm701319c (literal)
Alternative label
  • Leese MP; Jourdan FL; Gaukroger K; Mahon MF; Newman SP; Foster PA; Stengel C; Regis-Lydi S; Ferrandis E; Di Fiore A; De Simone G; Supuran CT; Purohit A; Reed MJ; Potter BV. (2008)
    Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents
    in Journal of medicinal chemistry
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Leese MP; Jourdan FL; Gaukroger K; Mahon MF; Newman SP; Foster PA; Stengel C; Regis-Lydi S; Ferrandis E; Di Fiore A; De Simone G; Supuran CT; Purohit A; Reed MJ; Potter BV. (literal)
Pagina inizio
  • 1295 (literal)
Pagina fine
  • 1308 (literal)
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  • 51 (literal)
Rivista
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  • Pubblicazione su rivista internazionale (literal)
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Medicinal Chemistry, Department of Pharmacy and Pharmacology & Sterix Ltd., and Department of Chemistry, UniVersity of Bath, Bath BA2 7AY, U.K.; Endocrinology and Metabolic Medicine and Sterix Ltd., Faculty of Medicine, Imperial College London, St. Mary's Hospital, London W2 1NY, U.K.; IPSEN System Biology, 91966 Les Ulis, France; Istituto di Biostrutture e Bioimmagini-CNR, Naples, Italy; Laboratorio di Chimica Bioinorganica, UniVersità degli Studi di Firenze, Florence, Italy (literal)
Titolo
  • Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents (literal)
Abstract
  • The synthesis, SAR, and preclinical evaluation of 17-cyanated 2-substituted estra-1,3,5(10)-trienes as anticancer agents are discussed. 2-Methoxy-17?-cyanomethylestra-1,3,5(10)-trien-3-ol (14), but not the related 2-ethyl derivative 7, and the related 3-O-sulfamates 8 and 15 display potent antiproliferative effects (MCF-7 GI50 300, 60 and 70 nM, respectively) against human cancer cells in vitro. Investigation of the SAR reveals that a sterically unhindered hydrogen bond acceptor attached to C-17 is most likely key to the enhanced activity. Compound 8 displayed significant in vitro antiangiogenic activity, and its ability to act as a microtubule disruptor was confirmed. Inhibitory activity of the sulfamate derivatives against steroid sulfatase and carbonic anhydrase II (hCAII) was also observed, and the interaction between 15 and hCAII was investigated by protein crystallography. The potential of these multimechanism anticancer agents was confirmed in vivo, with promising activity observed for both 14 and 15 in an athymic nude mouse MDAMB- 231 human breast cancer xenograft model. (literal)
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